Project Summary Schistosomiasis infects more than 207 million people worldwide. More than 250,000 people die annually from schistosome-associated complications. Treatment for schistosomiasis relies primarily on the drug, praziquantel, which has been in use for more than 30 years. Although our knowledge of schistosome parasites has expanded since the genome was sequenced in recent years, our understanding of schistosome development at the molecular level has been incremental, making the identification of rationally designed drug targets difficult. Therefore, it is important to begin to define the basic pathways important for schistosome viability. We hope to progress toward this goal by defining early genetic pathways necessary for schistosome development immediately after infecting a human host. This study will focus the Sex determining region Y-box 2 (Sox2) protein in schistosomes. Sox2 is a transcriptional activator that is expressed prior to blastulation in mammalian development and is necessary for embryogenesis. Sox2 expression is associated with pluripotency and stem cells, neuronal differentiation, gut development, and cancer. Although most mammalian studies on Sox2 have been analyzed in cell culture, schistosomes express this gene after infecting a mammalian host long after formation of a blastula. We will determine the effect of inappropriate temporal expression and down regulation of the Sox2 gene on potential Sox2 targets and on schistosome viability, with a particular emphasis on the development of the schistosome gut. We hypothesize that Sox2 is required for normal gut development in schistosomes. This study provides a novel opportunity to understand the effect of Sox2 at the organism level.